Lyophilization or freeze-drying is a drying technique employing freezing then sublimination of the water contained in the frozen product.
This process, although expensive, is being developed more and more, as it allows numerous substances to be dried without their properties altering. The principal applications are as follows:
preservation of fragile products of biological origin;
preservation and storage of food products, these products then being very easily dissolvable, freeze-drying giving these products a very aerated structure of which the surface of contact with the solvent is very large;
solution to the problem of packing if it is desired to introduce very small quantities of solid substances in flasks. In that case, the solution of the substance is introduced into the recipient and then freeze-dried, an adequate dilution allowing the solution to be very easily weighed;
solution to the problem of Galenicals by leading to the solidification of certain substances which will find a direct application in this presentation.
A cycle of freeze-drying comprises three steps:
freezing, operation during which the product to be dried is taken to a temperature of total solidification or eutectic temperature,
sublimation, during which the water passes directly from the solid state to the state of vapour and will be trapped in the solid state on a cold wall. During this operation, the partial vapour pressure above the product must be lower than the vapour pressure of the ice at the same temperature, the temperature of the product remaining lower than the eutectic temperature,
secondary drying. This phase is intended to eliminate the traces of water remaining in the product. To that end, it will be necessary to have the lowest possible partial pressure and the highest possible temperature of the product lower than that of its denaturation.
It follows from the foregoing that the shape of the product is set during the freezing process and that it will remain unchanged until the end of freeze-drying. Morever, it is absolutely indispensable that the temperature of the product remains lower than the eutectic temperature.
Freeze-drying may be carried out in two types of apparatus: the first consists of flasks in the atmosphere and connected to the enclosure in vacuo containing the trap. In this system, the substance is previously frozen in the flask placed to that end in a freezer. In this system, the calories necessary for sublimation are brought by the atmosphere. The second type of apparatus consists in shelves on which the product to be freeze-dried is placed. The product may be pre-frozen or frozen in situ on the shelves. When freezing is terminated, freeze-drying is carried out on the same shelves which will be heated so as to bring to the product the calories necessary for sublimation of the water.
This latter type of apparatus is at the present time the only one used on an industrial scale. In this case, freezing in situ may raise serious difficulties when the product is viscous and consequently heat exchanges are difficult. In that case, two phenomena may occur: on the one hand, during freezing, a hummock appears and, on the other hand, during freeze-drying, the formation on the surface of a film which is more compact than the rest of the product. This leads to a heterogeneous material being obtained, a defect rendering the product unusable when freeze-drying is used as means for shaping. These phenomena will occur all the more clearly as the thickness to be freeze-dried is greater.
The first phenomenon comes from the imprisonment of a certain quantity of liquid between an envelope of ice forming on the bottom, the walls of the plate containing the substance as well as on the surface of the product. The negative calories on the bottom and walls are brought by conduction from the freeze-drying shelf, whilst, on the surface of the product, they are brought essentially by radiation from the shelf above. When the imprisoned liquid begins to freeze, there is an increase in volume and the liquid passes through the frozen wall of the surface and forms a hummock which freezes (FIG. 1).
The second phenomenon, i.e. the formation of a film on the surface of the product is provoked by a defrosting due to a heating by radiation of the shelf of the freeze-drying apparatus located just above the freeze-drying plate, and to the absence of a sufficient heat conduction within the product. Such defrosting brings about liquefaction of the water of the product which is no longer sublimated but evaporates. This results in the formation of a more compact film on the surface of the product which renders the freeze-dried material heterogeneous.
Moreover, this film is relatively impermeable. It may in certain cases contribute to lengthening the freeze-drying time by slowing down the exchanges between the gas and the deeper layers of frozen product.
U.S. Pat. No. 4,501,719 relates to a freeze-drying apparatus comprising a plate laminate 14 provided with wells 12 in which the solutions 16 to be freeze-dried are disposed. Col. 2, lines 62 to 68 and col. 4, lines 50 to 58 mention the use of an insulator 43 disposed above the plate 14 containing the freeze-dried solutions disposed in the wells 12 (cf. FIG. 3). This insulator 43 is made of Styrofoam, with an intermediate plexiglass sheet 44. It is preferably enveloped in an aluminium foil to augment its insulation properties (cf. 4, lines 50 to 53).
According to this document, the use of a passive thermal shield is thus provided. However, in practice, it has appeared that such a passive thermal shield does not solve the technical problems set forth hereinabove and therefore presents the same drawbacks. In addition, the use of a passive thermal shield does not enable homogeneous and flat products to be obtained in the case of viscous solutions, particularly when they are in a considerably thick arrangement.
It is therefore an object of the present invention to solve the new technical problem of providing a solution for obtaining, by freeze-drying, freeze-dried products which are homogeneous or with greatly improved homogeneity, with respect to the products obtained by the heretofore known freeze-drying processes and apparatus.
It is another principal object of the present invention to solve the new technical problem of providing a process and an apparatus for freeze-drying various viscous products or solutions, which are very difficult to freeze-dry, enabling very homogeneous and flat products to be obtained.
It is another principal object of the present invention to solve the new technical problem of providing a process and apparatus for freeze-drying various products or solutions, particularly viscous solutions, even in a considerably thick arrangement, which results in homogeneous freeze-dried products.
It is yet another object of the invention to solve the new technical problem of providing a process and apparatus for freeze-drying various products or solutions, in particular viscous solutions which may be in a considerably thick arrangement, resulting in homogeneous products, which is of extremely simple design, with low manufacturing costs, and adapted to be used on an industrial scale.
All these new technical problems are solved for the first time by the present invention in simple manner and applicable on an industrial scale.